Antitumor effect of radiation therapy on orthotopic PDX models of human esophageal adenocarcinoma

Kiblitskaya AA, Goncharova AS, Anisimov AE, Snezhko AV, Dimitriadi SN, Maslov AA, Gevorkyan YA, Kolesnikov EN
About authors

National Medical Research Center of Oncology, Rostov-on-Don, Russia

Correspondence should be addressed: Alexandra A. Kiblitskaya
14 Liniya, 63, Rostov-on-Don, 344037; moc.liamg@dnaelabik

About paper

Author contribution: Kiblitskaya AA — data processing, manuscript preparation, technical editing, reference list, figures; Goncharova AS, Maslov AA — study concept and design, manuscript preparation; Anisimov AE — study concept and design, manuscript preparation, data acquisition, analysis and interpretation; Snezhko AV — content editing, manuscript preparation; Dimitriadi SN — data analysis and interpretation, technical editing; Gevorkyan YA — content editing; Kolesnikov EN — content and technical editing.

Ethical standards: the study fully complied with the principles of the Declaration of Helsinki; all requirements for animal housing were met; surgical interventions were conducted following the guidelines on the Care and Use of Laboratory Animals. The donors provided informed consent for their biological samples to be used in the study.

Received: 2021-09-16 Accepted: 2021-10-04 Published online: 2021-10-20

As a rule, esophageal adenocarcinoma develops in the lower esophagus. Life expectancy and survival rates depend on the cancer stage and the general health of the patient. Chemoradiotherapy is the most successful treatment approach to this type of cancer. The choice of optimal radiation doses for achieving the best possible therapeutic effect is still a challenge. The aim of this paper was to study effective radiation doses and assess response of human esophageal adenocarcinoma to radiation using a PDX model. The study was conducted in female Balb/c nude mice (n = 25). Fragments of the donor tumor were implanted into the cervical esophagus of immunodeficient mice. Effects of radiation on the obtained orthotopic xenografts were studied after each of 3 irradiation sessions (4, 6, 8, and 10 Gy in each of the experimental groups, respectively). First-passage xenografts reproduced the morphology of the donor tumor. The mean tumor volume differed significantly between the control group and the experimental groups exposed to 6, 8 or 10 Gy (р ≤ 0.01) after each irradiation session. Tumor growth delay was significant after exposure to the total dose of 18 Gy. The further radiation dose increase was ineffective. The reduction of tumor volume in the xenografts was correlated to the increase in the one-time radiation dose. The total dose over 18 Gy produced a detrimental effect on the hematopoietic system and blood biochemistry of the experimental mice.

Keywords: radiotherapy, esophageal adenocarcinoma, orthotopic xenograft, PDX-model, immunodeficient mouse